Translocator Protein 18 kDa-Targeted Total-Body PET Imaging Reveals Immune-Specific Vascular Inflammation in Large-Vessel Vasculitis: A Prospective Head-to-Head Comparison with ¹⁸F-FDG.

Abstract

Accurate assessment of vascular inflammation in large-vessel vasculitis (LVV) remains challenging, especially in patients with normal inflammatory markers or inconclusive ¹⁸F-FDG PET findings. The translocator protein 18 kDa (TSPO), a marker of inflammatory process, has emerged as a promising molecular target for imaging vascular inflammation in LVV. <b>Methods:</b> We prospectively enrolled 11 treatment-naïve patients with LVV and 11 healthy controls who underwent 90-min dynamic total-body ¹⁸F-DPA714 PET/CT imaging. Ten patients also underwent ¹⁸F-FDG PET/CT for direct comparison. We assessed SUVs, lesion-to-background ratios, and kinetic parameters using a 2-tissue compartment model (2T4K_vB). Peripheral blood samples from patients and controls were analyzed by flow cytometry to characterize the cellular sources of the TSPO signal. <b>Results:</b> ¹⁸F-DPA714 PET revealed that tracer uptake in patients with LVV was significantly higher than that in healthy controls (median SUV_mean, 0.81 [interquartile range (IQR), 0.64-0.98] vs. 0.54 [IQR, 0.44-0.64]; <i>P</i> = 0.000-0.043). Kinetic modeling using the 2T4K_vB compartment model further confirmed the specificity of TSPO binding, demonstrating elevated parameters of irreversible binding and total distribution volume in inflamed vascular segments. In head-to-head comparisons, ¹⁸F-DPA714 showed modestly but significantly higher vessel wall-to-lumen contrast relative to ¹⁸F-FDG (lesion-to-background ratio, 1.02 [IQR, 1.00-1.15] vs. 1.00 [IQR, 0.98-1.01]; <i>P</i> = 0.005-0.021). Among patients with relatively lower C-reactive protein levels (<58.04 mg/L; <i>n</i> = 5), ¹⁸F-DPA714 detected a significantly greater inflammatory burden than did ¹⁸F-FDG (inflammatory activity burden, 3,406.4 [IQR, 1,063.6-5,624.2] vs. 0 [IQR, 0-334.8]; <i>P</i> = 0.043), whereas no significant intertracer difference was observed in the high C-reactive protein group (≥58.04 mg/L, <i>n</i> = 5). In addition, flow cytometry of peripheral blood revealed that TSPO expression was predominantly localized to monocytes and neutrophils, supporting their contribution to the PET signal in patients. <b>Conclusion:</b> TSPO-targeted PET imaging complements and extends current approaches to assess vascular inflammation in LVV. By enabling sensitive detection of subclinical disease, it offers a promising platform for disease monitoring.